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Background: While many North American healthcare institutions are switching from Tuberculin Skin Test (TST) to Interferon-gamma release assays (IGRAs), there is relatively limited data on association between occupational tuberculosis (TB) risk factors and test positivity and/or patterns of test discordance. Methods: We recruited a cohort of Canadian health care workers (HCWs) in Montreal, and performed both TST and QuantiFERON-TB Gold In Tube (QFT) tests, and assessed risk factors and occupational exposure. Results: In a cross- sectional analysis of baseline results, the prevalence of TST positivity using the 10 mm cut-off was 5.7% (22/388, 95%CI: 3.6-8.5%), while QFT positivity was 6.2% (24/388, 95%CI: 4-9.1%). Overall agreement between the tests was poor (kappa = 0.26), and 8.3% of HCWs had discordant test results, most frequently TST2/QFT+ (17/388, 4.4%). TST positivity was associated with total years worked in health care, non-occupational exposure to TB and BCG vaccination received after infancy or on multiple occasions. QFT positivity was associated with having worked as a HCW in a foreign country. Conclusions: Our results suggest that LTBI prevalence as measured by either the TST or the QFT is low in this HCW population. Of concern is the high frequency of unexplainable test discordance, namely: TST2/QFT+ subjects, and the lack of any association between QFT positivity and clear-cut recent TB exposure. If these discordant results are indeed false positives, the use of QFT in lieu of TST in low TB incidence settings could result in overtreatment of uninfected individuals. [ABSTRACT FROM AUTHOR]